tbuckley/cabot-search huggingface dataset:
Keratinocyte-derived S100A9 modulates neutrophil infiltration and affects psoriasis-like skin and joint disease
Authors: Liliana F Mellor, Nuria Gago-Lopez, Latifa Bakiri, Felix N Schmidt, Björn Busse, Simon Rauber, Maria Jimenez, Diego Megías, Sergio Oterino-Sogo, Ricardo Sanchez-Prieto, Sergei Grivennikov, Xinzhu Pu, Julia Oxford, Andreas Ramming, Georg Schett, Erwin F Wagner
Journal: Annals of the Rheumatic Diseases (2022)

S100A9, an alarmin that can form calprotectin (CP) heterodimers with S100A8, is mainly produced by keratinocytes and innate immune cells. The contribution of keratinocyte-derived S100A9 to psoriasis (Ps) and psoriatic arthritis (PsA) was evaluated using mouse models, and the potential usefulness of S100A9 as a Ps/PsA biomarker was assessed in patient samples.
Combined nature and human selections reshaped peach fruit metabolome
Authors: Ke Cao, Bin Wang, Weichao Fang, Gengrui Zhu, Changwen Chen, Xinwei Wang, Yong Li, Jinlong Wu, Tang Tang, Zhangjun Fei, Jie Luo, Lirong Wang
Journal: Genome biology (2022)

Abstract Background Plant metabolites reshaped by nature and human beings are crucial for both their lives and human health. However, which metabolites respond most strongly to selection pressure at different evolutionary stages and what roles they undertake on perennial fruit crops such as peach remain unclear. Results Here, we report 18,052 significant locus-trait associations, 12,691 expression-metabolite correlations, and 294,676 expression quantitative trait loci (eQTLs) for peach. Our results indicate that amino acids accumulated in landraces may be involved in the environmental adaptation of peaches by responding to low temperature and drought. Moreover, the contents of flavonoids, the major nutrients in fruits, have kept decreasing accompanied by the reduced bitter flavor during both domestication and improvement stages. However, citric acid, under the selection of breeders’ and consumers’ preference for flavor, shows significantly different levels between eastern and western varieties. This correlates with differences in activity against cancer cells in vitro in fruit from these two regions. Based on the identified key genes regulating flavonoid and acid contents, we propose that more precise and targeted breeding technologies should be designed to improve peach varieties with rich functional contents because of the linkage of genes related to bitterness and acid taste, antioxidant and potential anti-cancer activity that are all located at the top of chromosome 5. Conclusions This study provides powerful data for future improvement of peach flavor, nutrition, and resistance in future and expands our understanding of the effects of natural and artificial selection on metabolites.
Emergence of H3N8 avian influenza viruses possessing tri-basic hemagglutinin cleavage sites in China
Authors: Feng Wen, Xingyu Zhang, Jinyue Guo, Zhipeng Liang, Qing Cheng, Congying Wang, Hai Yu, Yuguang Du, Shujian Huang, Jianjun Li, Yong Li
Journal: Journal of Infection (2022)
The use of fibroblasts as a valuable strategy for studying mitochondrial impairment in neurological disorders
Authors: Margrethe A. Olesen, Francisca Villavicencio-Tejo, Rodrigo A. Quintanilla
Journal: Translational Neurodegeneration (2022)

Neurological disorders (NDs) are characterized by progressive neuronal dysfunction leading to synaptic failure, cognitive impairment, and motor injury. Among these diseases, Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) have raised a significant research interest. These disorders present common neuropathological signs, including neuronal dysfunction, protein accumulation, oxidative damage, and mitochondrial abnormalities. In this context, mitochondrial impairment is characterized by a deficiency in ATP production, excessive production of reactive oxygen species, calcium dysregulation, mitochondrial transport failure, and mitochondrial dynamics deficiencies. These defects in mitochondrial health could compromise the synaptic process, leading to early cognitive dysfunction observed in these NDs. Interestingly, skin fibroblasts from AD, PD, HD, and ALS patients have been suggested as a useful strategy to investigate and detect early mitochondrial abnormalities in these NDs. In this context, fibroblasts are considered a viable model for studying neurodegenerative changes due to their metabolic and biochemical relationships with neurons. Also, studies of our group and others have shown impairment of mitochondrial bioenergetics in fibroblasts from patients diagnosed with sporadic and genetic forms of AD, PD, HD, and ALS. Interestingly, these mitochondrial abnormalities have been observed in the brain tissues of patients suffering from the same pathologies. Therefore, fibroblasts represent a novel strategy to study the genesis and progression of mitochondrial dysfunction in AD, PD, HD, and ALS. This review discusses recent evidence that proposes fibroblasts as a potential target to study mitochondrial bioenergetics impairment in neurological disorders and consequently to search for new biomarkers of neurodegeneration.
A health campaign and sunbed ban to reduce skin cancer: a good use of the healthcare budget
Journal: British Journal of Dermatology (2022)

Melanomas and other skin cancers are increasingly common in the UK, where more than 100,000 people get skin cancer each year. These cancers affect quality of life, and for over 2000 people per year in England are fatal. Treating these cancers also places a heavy burden on the National Health Service (NHS).
Leflunomide versus azathioprine for maintenance therapy of lupus nephritis: a prospective, multicentre, randomised trial and long-term follow-up
Authors: Qiong Fu, Chunmei Wu, Min Dai, Suli Wang, Jianhua Xu, Lie Dai, Zhijun Li, Lan He, Xiaochun Zhu, Lingyun Sun, Liangjing Lu, Chunde Bao
Journal: Annals of the Rheumatic Diseases (2022)

Objectives Previous studies have compared mycophenolate mofetil and azathioprine as maintenance therapy for lupus nephritis (LN). Leflunomide is an immunosuppressant widely used in the treatment of rheumatoid arthritis. The aim of this investigator-initiated study was to compare the efficacy and safety of leflunomide versus azathioprine as maintenance therapy for LN. Methods 270 adult patients with biopsy-confirmed active LN from 7 Chinese Rheumatology Centres were enrolled. All patients received induction therapy with 6–9 months of intravenous cyclophosphamide plus glucocorticoids. Patients who achieved complete response (CR) or partial response (PR) were randomised to receive prednisone in combination with leflunomide or azathioprine as maintenance therapy for 36 months. The primary efficacy endpoint was the time to kidney flare. Secondary outcomes included clinical parameters, extrarenal flare and adverse effects. Results A total of 215 patients were randomly allocated to the leflunomide group (n=108) and azathioprine group (n=107). Kidney flares were observed in 17 (15.7%) leflunomide-treated patients and 19 (17.8%) azathioprine-treated patients. Time to kidney flare did not statistically differ (leflunomide: 16 months vs azathioprine: 14 months, p=0.676). 24-hour proteinuria, serum creatinine, serum albumin, serum C3 and serum C4 improved similarly. Extrarenal flare occurred in two patients from the azathioprine group and one patient from the leflunomide group. The incidence of adverse events was similar in the 2 groups: leflunomide 56.5% and azathioprine 58.9%. Conclusions The efficacy and safety profile of leflunomide are non-inferior to azathioprine for maintenance therapy of LN. Leflunomide may provide a new candidate for maintenance therapy in patients with LN. Trial registration number NCT01172002 .
Immune checkpoint molecules in neuroblastoma: A clinical perspective
Authors: Anup S. Pathania, Philip Prathipati, Swati P. Murakonda, Ajay B. Murakonda, Ankit Srivastava, None Avadhesh, Siddappa N. Byrareddy, Don W. Coulter, Subash C. Gupta, Kishore B. Challagundla
Journal: Seminars in Cancer Biology (2022)
Cross-Platform Omics Prediction procedure: a statistical machine learning framework for wider implementation of precision medicine
Authors: Kevin Y. X. Wang, Gulietta M. Pupo, Varsha Tembe, Ellis Patrick, Dario Strbenac, Sarah-Jane Schramm, John F. Thompson, Richard A. Scolyer, Samuel Muller, Garth Tarr, Graham J. Mann, Jean Y. H. Yang
Journal: npj Digital Medicine (2022)

In this modern era of precision medicine, molecular signatures identified from advanced omics technologies hold great promise to better guide clinical decisions. However, current approaches are often location-specific due to the inherent differences between platforms and across multiple centres, thus limiting the transferability of molecular signatures. We present Cross-Platform Omics Prediction (CPOP), a penalised regression model that can use omics data to predict patient outcomes in a platform-independent manner and across time and experiments. CPOP improves on the traditional prediction framework of using gene-based features by selecting ratio-based features with similar estimated effect sizes. These components gave CPOP the ability to have a stable performance across datasets of similar biology, minimising the effect of technical noise often generated by omics platforms. We present a comprehensive evaluation using melanoma transcriptomics data to demonstrate its potential to be used as a critical part of a clinical screening framework for precision medicine. Additional assessment of generalisation was demonstrated with ovarian cancer and inflammatory bowel disease studies.
Novel intravesical bacterial immunotherapy induces rejection of BCG-unresponsive established bladder tumors
Authors: Eduardo Moreo, Santiago Uranga, Ana Picó, Ana Belén Gómez, Denise Nardelli-Haefliger, Carlos del Fresno, Ingrid Murillo, Eugenia Puentes, Esteban Rodríguez, Mar Vales-Gómez, Julian Pardo, David Sancho, Carlos Martín, Nacho Aguilo
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Intravesical BCG is the gold-standard therapy for non-muscle invasive bladder cancer (NMIBC); however, it still fails in a significant proportion of patients, so improved treatment options are urgently needed. Methods Here, we compared BCG antitumoral efficacy with another live attenuated mycobacteria, MTBVAC, in an orthotopic mouse model of bladder cancer (BC). We aimed to identify both bacterial and host immunological factors to understand the antitumoral mechanisms behind effective bacterial immunotherapy for BC. Results We found that the expression of the BCG-absent proteins ESAT6/CFP10 by MTBVAC was determinant in mediating bladder colonization by the bacteria, which correlated with augmented antitumoral efficacy. We further analyzed the mechanism of action of bacterial immunotherapy and found that it critically relied on the adaptive cytotoxic response. MTBVAC enhanced both tumor antigen-specific CD4 + and CD8 + T-cell responses, in a process dependent on stimulation of type 1 conventional dendritic cells. Importantly, improved intravesical bacterial immunotherapy using MBTVAC induced eradication of fully established bladder tumors, both as a monotherapy and specially in combination with the immune checkpoint inhibitor antiprogrammed cell death ligand 1 (anti PD-L1). Conclusion These results contribute to the understanding of the mechanisms behind successful bacterial immunotherapy against BC and characterize a novel therapeutic approach for BCG-unresponsive NMIBC cases.
Integrative molecular profiling identifies two molecularly and clinically distinct subtypes of blastic plasmacytoid dendritic cell neoplasm
Authors: Axel Künstner, Julian Schwarting, Hanno M. Witte, Veronica Bernard, Stephanie Stölting, Kathrin Kusch, Kumar Nagarathinam, Nikolas von Bubnoff, Eva Maria Murga Penas, Hartmut Merz, Hauke Busch, Alfred C. Feller, Niklas Gebauer
Journal: Blood Cancer Journal (2022)

Integrative molecular profiling identifies two molecularly and clinically distinct subtypes of blastic
GoPeaks: histone modification peak calling for CUT&amp;Tag
Authors: William M. Yashar, Garth Kong, Jake VanCampen, Brittany M. Curtiss, Daniel J. Coleman, Lucia Carbone, Galip Gürkan Yardimci, Julia E. Maxson, Theodore P. Braun
Journal: Genome biology (2022)

Genome-wide mapping of histone modifications is critical to understanding transcriptional regulation. CUT&Tag is a new method for profiling histone modifications, offering improved sensitivity and decreased cost compared with ChIP-seq. Here, we present GoPeaks, a peak calling method specifically designed for histone modification CUT&Tag data. We compare the performance of GoPeaks against commonly used peak calling algorithms to detect histone modifications that display a range of peak profiles and are frequently used in epigenetic studies. We find that GoPeaks robustly detects genome-wide histone modifications and, notably, identifies a substantial number of H3K27ac peaks with improved sensitivity compared to other standard algorithms.
A cure for everything and nothing? Local partnerships for improving health in England
Authors: Hugh Alderwick, Andrew Hutchings, Nicholas Mays
Journal: BMJ (2022)

The NHS in England is being reorganised under the Health and Care Act 2022-the biggest overhaul of NHS rules and structures in a decade. 1 2 A key aim of the changes-introduced on 1 July 2022-is to encourage collaboration between NHS, local government, and other agencies to improve health and reduce health inequalities. 3England will be divided into 42 area based integrated care systems, bringing together NHS organisations, social care, public health, and others to plan and coordinate local services for populations of around 500 000 to three million people.
Mast cell chymase regulates extracellular matrix remodeling-related events in primary human small airway epithelial cells
Authors: Xinran O. Zhao, Christian P. Sommerhoff, Aida Paivandy, Gunnar Pejler
Journal: Journal of Allergy and Clinical Immunology (2022)

Mast cells are implicated in the pathogenesis of asthma, but the underlying mechanisms are not fully elucidated. Under asthmatic conditions, mast cells can relocalize to the epithelial layer and may thereby affect the functional properties of the airway epithelial cells.Activated mast cells release large quantities of proteases from their secretory granules, including chymase and tryptase. Here we investigated whether these proteases may affect airway epithelial cells.Primary small airway epithelial cells were treated with tryptase or chymase, and the effects on epithelial cell viability, proliferation, migration, cytokine output, and transcriptome were evaluated.Airway epithelial cells were relatively refractory to tryptase. In contrast, chymase had extensive effects on multiple features of the epithelial cells, with a particular emphasis on processes related to extracellular matrix (ECM) remodeling. These included suppressed expression of ECM-related genes such as matrix metalloproteinases, which was confirmed at the protein level. Further, chymase suppressed the expression of the fibronectin gene and also caused degradation of fibronectin released by the epithelial cells. Chymase was also shown to suppress the migratory capacity of the airway epithelial cells and to degrade the cell-cell contact protein E-cadherin on the epithelial cell surface.Our findings suggest that chymase may affect the regulation of ECM remodeling events mediated by airway epithelial cells, with implications for the impact of mast cells in inflammatory lung diseases such as asthma.
Monkeypox and pan-resistant Campylobacter spp infection in Entamoeba histolytica and Chlamydia trachomatis re-infection in a man who have sex with men
Authors: Angelo Roberto Raccagni, Davide Mileto, Diana Canetti, Andrea Marco Tamburini, Alberto Rizzo, Elena Bruzzesi, Antonella Castagna, Silvia Nozza
Journal: Journal of Infection (2022)
The future of PSMA PET and WB MRI as next-generation imaging tools in prostate cancer
Authors: Yishen Wang, Joao R. Galante, Athar Haroon, Simon Wan, Asim Afaq, Heather Payne, Jamshed Bomanji, Sola Adeleke, Veeru Kasivisvanathan
Journal: Nature Reviews Urology (2022)
Estetrol/Drospirenone: A Review in Oral Contraception
Authors: Arnold Lee, Yahiya Y. Syed
Journal: Drugs (2022)

Estetrol/drospirenone is a combined oral contraceptive (COC) with a plant-synthesised foetal oestrogen (estetrol) and a well-established progestin (drospirenone). In preclinical models, estetrol has lower binding affinity for the oestrogen receptor-α (ER-α) in contrast to estradiol and has antagonistic properties against membrane ER-α in several tissues, including the breast, while retaining agonistic activity on receptors located in the nucleus. The low oestrogenicity of estetrol may potentially contribute to reduced thrombotic risk. Estetrol/drospirenone was an effective contraceptive in phase II and III clinical trials, with regular and predictable bleeding cycles maintained in the majority of women. Estetrol/drospirenone was generally well-tolerated with metrorrhagia reported as the most common treatment-related adverse event, which is consistent with other COCs. Cases of migraines with aura (or severe migraines), deep vein thrombosis, hyperkalaemia and depression were rarely reported during the phase III trials. Overall, estetrol/drospirenone is an effective and generally well-tolerated COC, with a potentially reduced risk of thrombosis. In 2019, an estimated 44% of women aged 15–49 years worldwide used modern contraception methods, and in these women using modern methods, 18% used an oral contraceptive. Estetrol/drospirenone is a combined oral contraceptive (COC) which uses estetrol, a plant-synthesised oestrogen naturally produced by the human foetal liver during pregnancy, in combination with drospirenone, a well-known progestin. Combined, these hormones suppress ovulation, which constitutes their primary mode of action in preventing pregnancy. As estetrol has weaker oestrogen-related effects, it may potentially reduce the risk for blood clots. Estetrol/drospirenone was an effective contraceptive in clinical trials, and most women had regular and predictable bleeding cycles. Metrorrhagia (i.e. abnormal bleeding) was the most commonly reported treatment-related adverse effect; however, this is a common issue with hormonal contraceptives. Cases of severe migraine headaches, deep vein thrombosis, high potassium levels or depression were rarely reported during clinical trials. Estetrol/drospirenone is an effective oral contraceptive, which may offer a contraceptive option with a lower risk for blood clots. However, further research is required to confirm the reduced risk of clotting.
Intravenous tenecteplase compared with alteplase for acute ischaemic stroke in Canada (AcT): a pragmatic, multicentre, open-label, registry-linked, randomised, controlled, non-inferiority trial
Authors: Bijoy K Menon, Brian H Buck, Nishita Singh, Yan Deschaintre, Mohammed A Almekhlafi, Shelagh B Coutts, Sibi Thirunavukkarasu, Houman Khosravani, Ramana Appireddy, Francois Moreau, Gord Gubitz, Aleksander Tkach, Luciana Catanese, Dar Dowlatshahi, George Medvedev, Jennifer Mandzia, Aleksandra Pikula, Jai Shankar, Heather Williams, Thalia S Field, Alejandro Manosalva, Muzaffar Siddiqui, Atif Zafar, Oje Imoukhuede, Gary Hunter, Andrew M Demchuk, Sachin Mishra, Laura C Gioia, Shirin Jalini, Caroline Cayer, Stephen Phillips, Elsadig Elamin, Ashkan Shoamanesh, Suresh Subramaniam, Mahesh Kate, Gregory Jacquin, Marie-Christine Camden, Faysal Benali, Ibrahim Alhabli, Fouzi Bala, MacKenzie Horn, Grant Stotts, Michael D Hill, David J Gladstone, Alexandre Poppe, Arshia Sehgal, Qiao Zhang, Brendan Cord Lethebe, Craig Doram, Ayoola Ademola, Michel Shamy, Carol Kenney, Tolulope T Sajobi, Richard H Swartz
Journal: The Lancet (2022)
关于意大利黑色素瘤患者生存率提高原因的研究
Journal: British Journal of Dermatology (2022)

数十年来，黑色素瘤生存率在意大利及许多其他国家不断提高，研究者认为这是因为该疾病早期检测的进步，肿瘤在变厚之前便被发现。本研究希望了解这是否是 2003 至 2017 年间意大利黑色素瘤生存率提高的唯一原因。
Layered protein nanoparticles containing influenza B HA stalk induced sustained cross-protection against viruses spanning both viral lineages
Authors: Yufeng Song, Wandi Zhu, Ye Wang, Lei Deng, Yao Ma, Chunhong Dong, Gilbert X. Gonzalez, Joo Kim, Lai Wei, Sang-Moo Kang, Bao-Zhong Wang
Journal: Biomaterials (2022)
Exosomes decorated with a recombinant SARS-CoV-2 receptor-binding domain as an inhalable COVID-19 vaccine
Authors: Zhenzhen Wang, Kristen D. Popowski, Dashuai Zhu, Blanca López de Juan Abad, Xianyun Wang, Mengrui Liu, Halle Lutz, Nicole De Naeyer, C. Todd DeMarco, Thomas N. Denny, Phuong-Uyen C. Dinh, Zhenhua Li, Ke Cheng
Journal: Nature Biomedical Engineering (2022)
Efficacy and safety of upadacitinib for active ankylosing spondylitis refractory to biological therapy: a double-blind, randomised, placebo-controlled phase 3 trial
Authors: Désirée van der Heijde, Xenofon Baraliakos, Joachim Sieper, Atul Deodhar, Robert D Inman, Hideto Kameda, Xiaofeng Zeng, Yunxia Sui, Xianwei Bu, Aileen L Pangan, Peter Wung, In-Ho Song
Journal: Annals of the Rheumatic Diseases (2022)

Objectives To evaluate the efficacy and safety of upadacitinib, a Janus kinase inhibitor, in patients with active ankylosing spondylitis (AS) with an inadequate response (IR) to biological disease-modifying antirheumatic drugs (bDMARDs). Methods Adults with active AS who met modified New York criteria and had an IR to one or two bDMARDs (tumour necrosis factor or interleukin-17 inhibitors) were randomised 1:1 to oral upadacitinib 15 mg once daily or placebo. The primary endpoint was Assessment of SpondyloArthritis international Society 40 (ASAS40) response at week 14. Sequentially tested secondary endpoints included Ankylosing Spondylitis Disease Activity score, Spondyloarthritis Research Consortium of Canada MRI spine inflammation score, total back pain, nocturnal back pain, Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Metrology Index and Maastricht Ankylosing Spondylitis Enthesitis Score. Results are reported from the 14-week double-blind treatment period. Results A total of 420 patients with active AS were randomised (upadacitinib 15 mg, n=211; placebo, n=209). Significantly more patients achieved the primary endpoint of ASAS40 at week 14 with upadacitinib vs placebo (45% vs 18%; p&lt;0.0001). Statistically significant improvements were observed with upadacitinib vs placebo for all multiplicity-controlled secondary endpoints (p&lt;0.0001). Adverse events were reported for 41% of upadacitinib-treated and 37% of placebo-treated patients through week 14. No events of malignancy, major adverse cardiovascular events, venous thromboembolism or deaths were reported with upadacitinib. Conclusion Upadacitinib 15 mg was significantly more effective than placebo over 14 weeks of treatment in bDMARD-IR patients with active AS. No new safety risks were identified with upadacitinib. Trial registration number NCT04169373 .
Structural variants shape driver combinations and outcomes in pediatric high-grade glioma
Authors: Frank P. B. Dubois, Ofer Shapira, Noah F. Greenwald, Travis Zack, Jeremiah Wala, Jessica W. Tsai, Alexander Crane, Audrey Baguette, Djihad Hadjadj, Ashot S. Harutyunyan, Kiran H. Kumar, Mirjam Blattner-Johnson, Jayne Vogelzang, Cecilia Sousa, Kyung Shin Kang, Claire Sinai, Dayle K. Wang, Prasidda Khadka, Kathleen Lewis, Lan Nguyen, Hayley Malkin, Patricia Ho, Ryan O’Rourke, Shu Zhang, Rose Gold, Davy Deng, Jonathan Serrano, Matija Snuderl, Chris Jones, Karen D. Wright, Susan N. Chi, Jacques Grill, Claudia L. Kleinman, Liliana C. Goumnerova, Nada Jabado, David T. W. Jones, Mark W. Kieran, Keith L. Ligon, Rameen Beroukhim, Pratiti Bandopadhayay
Journal: Nature Cancer (2022)